The major objectives of this research plan are: (1) to study the abnormal regulation of antibody production in newly diagnosed untreated patients with non-Hodgkin's malignant lymphomas and (2) to study 12-0-tetradecanoylphorbol-13 acetate (TPA)-induced changes in the phenotype and function of malignant cells. The preliminary data indicate that an intrinsic defect exists in seemingly normal B lymphocytes from uninvolved peripheral blood in patients with malignant lymphomas. This defect can be responsible for lack of hypergammaglobulinemia in patients whose T lymphocytes show significantly increased helper activity in vitro. Immunoglobulin secretion in autologous and allogeneic mixtures of highly purified malignant or "normal" B lymphocytes and T lymphocytes will be measured by newly developed plaque-forming microassay, as well as by previously used double antibody radioimmunoassay. Tumor promoter, TPA, will be introduced into these studies because it was shown to induce in short-time culture the expression of maturation markers on malignant and normal cells. Recently, we reported TPA-induced changes in immunoregulation of immunoglobulin secretion by normal peripheral blood lymphocytes. We plan to continue these studies using malignant cells from patients with leukemias and lymphomas.